This project proposes the use of missense suppression as a means of obtaining tRNAs with mutationally altered functions and interactions. It calls for the utilization of mutations involving known codon changes at one position of the tryptophan synthetase alpha subunit, and knowledge of the behavior of (virtually) all amino acids at that position, to obtain the directed mutational conversion of glycine tRNA and other tRNAs to new coding and amino acid accepting specificities. It aims at the preliminary characterization of the altered tRNAs by column chromatography, determination of changes in nucleotide sequence, and correlation of altered sequence with altered functions and other changes in tRNA structure and interactions. The results of these studies are necessary to form the basis for the possibility of "tRNA therapy", whereby specifically altered suppressor tRNA molecules may be employed to phenotypically correct defects in human cells subject to premature ageing or neoplastic disease.